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2018 | 23 |

Tytuł artykułu

Effects of calcium Ionophore A23187 on the apoptosis of hepatic stellate cells stimulated by transforming growth factor-β1

Warianty tytułu

Języki publikacji

EN

Abstrakty

EN
Background: Our previous study showed that during in vitro experiments changes in calcium concentration were associated with apoptosis. We presumed that the calcium ion might play a role as intermediate messenger for apoptosis-related genes. No such evidence has been reported in the literature. Here, we investigate the effect of calcium ionophore A23187 on the apoptosis of rat hepatic stellate cells (HSCs) stimulated by transforming growth factor-β1 (TGF-β1) to explore the mechanism of apoptosis through the endoplasmic reticulum stress pathway. Methods: The apoptotic rate was determined using flow cytometry. The changes in Ca2+ level in HSCs were examined with laser confocal microscopy. The expressions of caspase-12 GRP78 and caspase-9 were assayed via western blot. Results: The respective apoptosis rates for the blank group, the TGF-β1 group and the TGF-β1 + low, medium and high dose calcium ionophore A23187 groups were 3. 40 ± 0.10%, 1.76 ± 0.12%, 5.86 ± 0.31%, 11.20 ± 0.48% and 15.08 ± 0.75%, with significant differences between the groups (p < 0.05). The concentration of Ca2+ and the expression of the GRP78, caspase-9 and caspase-12 proteins significantly increased with increasing calcium ionophore A23187 doses (p < 0.05). Conclusion: Calcium ionophore A23187 increased intracellular Ca2+ and activated endoplasmic reticulum stress, which promoted HSC apoptosis.

Słowa kluczowe

Wydawca

-

Rocznik

Tom

23

Opis fizyczny

p.1-9,fig.,ref.

Twórcy

autor
  • Department of School of Public Health, North China University of Science and Technology, Hebei, Tang Shan 063000, China
autor
  • Department of School of Public Health, North China University of Science and Technology, Hebei, Tang Shan 063000, China
autor
  • Department of School of Public Health, North China University of Science and Technology, Hebei, Tang Shan 063000, China
autor
  • Department of School of Public Health, North China University of Science and Technology, Hebei, Tang Shan 063000, China
autor
  • Department of School of Public Health, North China University of Science and Technology, Hebei, Tang Shan 063000, China
autor
  • Department of School of Public Health, North China University of Science and Technology, Hebei, Tang Shan 063000, China

Bibliografia

  • 1. Pereira TN, Walsh MJ, Lewindon PJ. Paediatric cholestatic liver disease:Diagnosis,assessment of disease progression and mechanisms of fibrogenesis. World J Gastrointest Pathophysio. 2010;1(2):69–84.
  • 2. Erkan M, Weis N, Pan Z. Organ-,inflammation- and cancer specific transcriptional fingerprints of pancreatic and hepatic stellate cells. Mol Cancer. 2010;9:88.
  • 3. Zhou W-c, Zhang Q-B, Liang Q. Pathogenesis of liver cirrhosis. World J Gastroenterol. 2014;20(23):7312–24.
  • 4. Weiskirchen R, Tacke F. Cellular and molecular functions of hepatic stellate cells in inflammatory responses and liver immunology. Hepatobiliary Surg Nutr. 2014;3(6):344–63.
  • 5. Sharma V, Kaur R, Bhatnagar A, et al. Low-pH-induced apoptosis: role of endoplasmic reticulum stress-induced calcium permeability and mitochondria-dependent signaling. Cell Stress Chaperones. 2015;20(3):431–40.
  • 6. Montague K, Malik B, Gray AL, et al. Endoplasmic reticulum stress in spinal and bulbar muscular atrophy: a potential target for therapy. Brain. 2014;137(7):1894–906.
  • 7. Liu Y, Han X-j, Liu M-h. Three-day-old human unfertilized oocytes after in vitro fertilization/intracytoplasmic sperm injection can be activated by calcium Ionophore A23187 or strontium chloride and develop to blastocysts. Cell Reprogram. 2014;16(4):276–80.
  • 8. Yonghong X, Dianwu L. Effect of transforming growth factor - β1 antibody on intracellular calcium concentration in hepatic stellate cells. J FourthMilMed Univ. 2005;26(17):1558-561.
  • 9. Bahar E, Kim H, Yoon H. ER stress-mediated signaling: action potential and Ca2+ as key players. Int J Mol Sci. 2016; 17(9):1558.
  • 10. Yang K, Qiang L, Yaining Z. A23187 induced HL-60 differentiation into dendritic cells. J Sichuan University (Medical Sciences). 2007;38(2):209–12.
  • 11. Axel H. Schönthal.Endoplasmic reticulum stress: its role in disease and novel prospects for therapy. Scientifica (Cairo). 2012:857516.
  • 12. Cho H, Wu M, Zhang L, et al. Signaling dynamics of palmitate-induced ER stress responses mediated by ATF4 in HepG2 cells. BMC Syst Biol. 2013;7(1):9.
  • 13. Sun Y, Liu G, Song T, et al. Upregulation of GRP78 and caspase-12 in diastolic failing hea. Acta Biochim Pol. 2008; 55(3):511–6.
  • 14. Kim EM, Shin EJ, Choi JH, et al. Matrix metalloproteinase-3 is increased and participates in neuronal apoptotic signalingdownstream of caspase-12 during endoplasmic reticulum stress. J Biol Chem. 2010;285(22):16444–52.
  • 15. Xie Q, Khaoustov VI, Chung CC, et al. Effect of tauroursodeoxycholic acid on ER stress_induced Caspase-12 activation. Hepatology. 2002;36(3):592–601.
  • 16. Nakagawa T, Zhu H, Morishima N, et al. Caspase-12 mediates ER_specific apoptosis and cytotoxicity by amyloid_β. Nature. 2000;403(6765):98–103.

Typ dokumentu

Bibliografia

Identyfikatory

Identyfikator YADDA

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